Differential requirements for ERK1/2 and p38 MAPK activation by thrombin in T cells.: Role of P59Fyn and PKCε

被引:29
作者
Maulon, L
Mari, B
Bertolotto, C
Ricci, JE
Luciano, F
Belhacene, N
Deckert, M
Baier, G
Auberger, P
机构
[1] INSERM, U526, F-06107 Nice 2, France
[2] Univ Innsbruck, Inst Med Biol & Human Genet, A-6020 Innsbruck, Austria
[3] Hop Archet, INSERM U343, Nice, France
关键词
T lymphocytes; thrombin; Src kinases; PKCs; MAP kinases;
D O I
10.1038/sj.onc.1204266
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Activation of the mitogen-activated protein kinase (MAPK) cascade is a well documented mechanism for the G-protein-coupled receptors, Here, we have analysed the requirements for ERKs and p38 MAPK activation by thrombin in Jurkat T cells. We show that thrombin-mediated ERKs activation requires both PTK and PKC activities, whereas p38 MAPK activation is dependent only on PTKs, Thrombin-induced ERK and p38 MAPK activation was more pronounced in p56Lck deficient cells indicating that this PTK exerts a negative control on MAPK activity. Accordingly, overexpression of p50 Csk a kinase that inactivates p56Lck induced constitutive activation of ERKs, Requirement for a Src kinase was evidenced by expression of a constitutively active form of p59Fyn in Jurkat cells. Besides its effect on tyrosine phosphorylation events, thrombin also triggered a rapid and robust redistribution of PKC epsilon and delta from the cytosol to the membrane. Expression of constitutively active and dominant negative PKC epsilon demonstrates the pivotal role of this PKC isoform in ERKs activation by thrombin, These data are consistent with a model where thrombin induces ERK activation via both PKC-dependent and independent pathways, whereas p38 MAPK activation requires only PTKs, The PKC-independent pathway requires Src kinases other than p56Lck more likely p59Fyn, while the PKC-dependent mechanism depends on PKC epsilon.
引用
收藏
页码:1964 / 1972
页数:9
相关论文
共 43 条
[1]   REQUIREMENT FOR INTEGRATION OF SIGNALS FROM 2 DISTINCT PHOSPHORYLATION PATHWAYS FOR ACTIVATION OF MAP KINASE [J].
ANDERSON, NG ;
MALLER, JL ;
TONKS, NK ;
STURGILL, TW .
NATURE, 1990, 343 (6259) :651-653
[2]  
AUTERO M, 1996, MOL CELL BIOL, V16, P1842
[3]  
Bjorkoy G, 1997, J BIOL CHEM, V272, P11557
[4]  
BRANCH DR, 1995, J IMMUNOL, V154, P3678
[5]   EPIDERMAL GROWTH-FACTOR REGULATES P21(RAS) THROUGH THE FORMATION OF A COMPLEX OF RECEPTOR, GRB2 ADAPTER PROTEIN, AND SOS NUCLEOTIDE EXCHANGE FACTOR [J].
BUDAY, L ;
DOWNWARD, J .
CELL, 1993, 73 (03) :611-620
[6]   REGULATION OF RAS-MEDIATED SIGNALING - MORE THAN ONE-WAY TO SKIN A CAT [J].
BURGERING, BMT ;
BOS, JL .
TRENDS IN BIOCHEMICAL SCIENCES, 1995, 20 (01) :18-22
[7]   Role of diacylglycerol-regulated protein kinase C isotypes in growth factor activation of the Raf-1 protein kinase [J].
Cai, H ;
Smola, U ;
Wixler, V ;
EisenmannTappe, I ;
DiazMeco, MT ;
Moscat, J ;
Rapp, U ;
Cooper, GM .
MOLECULAR AND CELLULAR BIOLOGY, 1997, 17 (02) :732-741
[8]  
CHEN YH, 1994, J BIOL CHEM, V269, P27372
[9]  
CONWAY AM, 1999, BIOCHEM J, P171
[10]   Adaptor function for the Syk kinases interacting protein 3BP2 in IL-2 gene activation [J].
Deckert, M ;
Tartare-Deckert, S ;
Hernandez, J ;
Rottapel, R ;
Altman, A .
IMMUNITY, 1998, 9 (05) :595-605